Goldsmith Juliet, Levine Beth, Debnath Jayanta
Department of Pathology, Helen Diller Family Comprehensive Cancer Center and Biomedical Science Graduate Program, University of California, San Francisco, California, USA.
Departments of Internal Medicine and Microbiology, Center for Autophagy Research, and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Methods Enzymol. 2014;542:25-57. doi: 10.1016/B978-0-12-416618-9.00002-9.
The metabolism of malignant cells is profoundly altered in order to maintain their survival and proliferation in adverse microenvironmental conditions. Autophagy is an intracellular recycling process that maintains basal levels of metabolites and biosynthetic intermediates under starvation or other forms of stress, hence serving as an important mechanism for metabolic adaptation in cancer cells. Although it is widely acknowledged that autophagy sustains metabolism in neoplastic cells under duress, many questions remain with regard to the mutual relationship between autophagy and metabolism in cancer. Importantly, autophagy has often been described as a "double-edged sword" that can either impede or promote cancer initiation and progression. Here, we overview such a dual function of autophagy in tumorigenesis and our current understanding of the coordinated regulation of autophagy and cancer cell metabolism in the control of tumor growth, progression, and resistance to therapy.
恶性细胞的代谢发生了深刻改变,以便在不利的微环境条件下维持其存活和增殖。自噬是一种细胞内循环过程,在饥饿或其他形式的应激下维持代谢物和生物合成中间体的基础水平,因此是癌细胞代谢适应的重要机制。尽管人们普遍认识到自噬在胁迫下维持肿瘤细胞的代谢,但关于癌症中自噬与代谢之间的相互关系仍有许多问题。重要的是,自噬常被描述为一把“双刃剑”,它既可以阻碍也可以促进癌症的发生和发展。在此,我们概述自噬在肿瘤发生中的这种双重功能,以及我们目前对自噬与癌细胞代谢在控制肿瘤生长、进展和治疗抗性方面的协调调节的理解。